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Long-term administration of L-DOPA does not damage dopaminergic neurons in the mouse

Laboratory of Neuroendocrine Regulation, Department of Nutrition and Food Science, Massachusetts Institute of Technology, Cambridge, MA (Drs. Helti, Melamed, Bhawan, and Wurtman), and the Department of Pathology, University of Massachusetts Medical School, Worcester, MA (Dr. Bhawan).

To examine the possibility that long-term L-DOPA therapy may be toxic to and destroy nigrostriatal dopaminergic neurons, mice were given large doses of L-DOPA (200 mg per animal per day) for 18 months. L-DOPA treatment was then discontinued to allow washout of drug from brain; 8 days later, L-DOPA was undetectable in corpora striata. Biochemical indices of the integrity of nigrostriatal neurons (striatal dopamine and DOPAC concentrations and activities of tyrosine hydroxylase and DOPA decarboxylase) were equal in DOPA-treated and control mice, suggesting that prolonged L-DOPA administration did not damage nigrostriatal neurons.

Address correspondence and reprint requests to Dr. Hefti, Max-Planck-Institut für Psyehiatrie, Abt. Neurochemie, Am Klopferspitz 18 a, D-8033 Martinsrid, West Germany.

This study was supported in part by GRSIBRS Institutional Fund 6-32963 and by the American Parkinson's Disease Association.

Accepted for publication December 1, 1980.

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